الفهرس 
AIM OF THE WORKيوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
This study was designed to explore the expected role of
colon cancer stem cells (CSCs) during the chemicallyinduced
mouse colon carcinogenesis with/or without the
treatment with a targeted therapeutic (anti-COX-2) drug,
celecoxib. Two experiments were performed, the first, a
short term 16- week colon carcinogenesis bioassay and the
other was a 32- week colon cancer bioassay. Celecoxib
treatment has lowered the numbers of aberrant crypt foci
(ACF), the well known biomarker of colon carcinogenesis,
as well as the tumors’ volumes and multiplicities. The
immunohistochemical proliferating cell nuclear antigen
(PCNA) labeling indexes LI (%) were down-regulated after
treatment by Celecoxib. Also, the expression patterns of
CD133and CD44, known to be associated with CSCs,
showed differential expression patterns depending on the
stage of carcinogenesis and celecoxib treatment. The flow
cytometric analysis revealed that the number of CD133
cells was increased in the colonic epithelium of mice after
16weeks, however, the number of CD44 but not CD133
cells was increased after 32 weeks. Moreover, the
Aldehyde dehydrogenase-1 activity levels, a known CSC
marker in colonic epithelium, was down-regulated after 16
weeks, but up-regulated after 32 weeks. The data have also
shown that celecoxib has modulated the mRNA expression
levels of APC and COX-2 genes, which are directly related
to colon cancer. Thus, the specific markers and CSC
populations targeted by this drug may vary depending on
the genetic and phenotypic stages of carcinogenesis. This
could be useful during specific treatment and targeted
therapy for colon cancer patients.
Key words: Colon cancer, ACF, mice, 1,2-
Dimethylhydrazine, cancer stem cells, ALDH1, CD44,
CD133, PCNA, COX-2, APC.